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DNA representation © AK-Brunschweiger​/​TU Dort­mund


Small organic compounds that bind to proteins and modulate their function are called bioactive small mol­ecules. They serve as drugs, starting points for drug development, and probes for chemical biology. The identification of bioactive small mol­ecules is one of the most critical steps in a drug dis­cov­ery program. It is a principal task of medicinal chemists. High throughput screening (HTS), i.e. the screening of large compound libraries at disease-re­le­vant protein targets has proven its value to discover bioactive mol­ecules. These may serve as starting points in drug development programs or as probes in chemical biology. New in­no­va­ti­ve and broadly applicable concepts to screen libraries of small mol­ecules at disease-re­le­vant proteins are badly needed. The concept to synthesize and pool large combinatorial DNA-encoded small molecule library and to screen the whole encoded library as a pool at immobilized protein targets in a single selection experiment is an in­no­va­ti­ve approach to bring HTS into academia.
Sequencing of the human genome provided the protein-coding sequences of all genes, in­clu­ding that subset of proteins capable of binding low molecular weight compounds, the so-called “druggable genome”. Typical mem­bers of the “druggable genome”, i.e. traditional drug targets, are for example G protein-coupled receptors and enzymes such as kinases. However, the number of proteins associated with diseases is much larger than the druggable genome. Many disease-related proteins, for instance those that take part in protein-protein interactions, are promising, yet difficult targets in drug re­search. Screening of large DNA-encoded libraries holds promise to identify small molecule ligands for these difficult protein targets.

What are our methods?

Methods of the Brunschweiger-Group © AK-Brunschweiger​/​TU Dort­mund

Encoding of small mol­ecules allows for pooling of small molecule libraries. Putative bioactive small mol­ecules can be identified through an efficient selection assay:

  1. Incubation of a large pooled encoded small molecule library with an immobilized target protein
  2. Washing steps to remove the non-binding small mol­ecules
  3. PCR-amplification of the selected small mol­ecules and Illumina sequencing to identify the protein binders
  4. Follow-up assays for validation of protein binders and elucidation of mode of action

We are applying a broad range of methods from two very different worlds: chem­is­try and molecular biology.

  • synthesize functionalized small molecule scaffolds by organic preparative chem­is­try
  • couple these scaffolds to DNA
  • perform combinatorial chem­is­try on the DNA-coupled scaffolds
  • develop novel DNA-compatible chemical methods to furnish the library
  • use methods from molecular biology to encode each chemical step
  • develop novel selection assay approaches

in order to

  • obtain a large, pooled small molecule library with hundreds of thousands of mem­bers
  • screen the pooled library at promising drug targets, also from collaboration partners,

to identify novel bioactive small mol­ecules.

Location & approach

The campus of TU Dort­mund Uni­ver­sity is located close to interstate junction Dort­mund West, where the Sauerlandlinie A 45 (Frankfurt-Dort­mund) crosses the Ruhrschnellweg B 1 / A 40. The best interstate exit to take from A 45 is "Dort­mund-Eichlinghofen" (closer to Cam­pus Süd), and from B 1 / A 40 "Dort­mund-Dorstfeld" (closer to Cam­pus Nord). Signs for the uni­ver­si­ty are located at both exits. Also, there is a new exit before you pass over the B 1-bridge leading into Dort­mund.

To get from Cam­pus Nord to Cam­pus Süd by car, there is the connection via Vo­gel­pothsweg/Baroper Straße. We recommend you leave your car on one of the parking lots at Cam­pus Nord and use the H-Bahn (suspended monorail system), which conveniently connects the two campuses.

TU Dort­mund Uni­ver­sity has its own train station ("Dort­mund Uni­ver­si­tät"). From there, suburban trains (S-Bahn) leave for Dort­mund main station ("Dort­mund Hauptbahnhof") and Düsseldorf main station via the "Düsseldorf Airport Train Station" (take S-Bahn number 1, which leaves every 20 or 30 minutes). The uni­ver­si­ty is easily reached from Bo­chum, Essen, Mülheim an der Ruhr and Duis­burg.

You can also take the bus or subway train from Dort­mund city to the uni­ver­si­ty: From Dort­mund main station, you can take any train bound for the Station "Stadtgarten", usually lines U41, U45, U 47 and U49. At "Stadtgarten" you switch trains and get on line U42 towards "Hombruch". Look out for the Station "An der Palmweide". From the bus stop just across the road, busses bound for TU Dort­mund Uni­ver­sity leave every ten minutes (445, 447 and 462). Another option is to take the subway routes U41, U45, U47 and U49 from Dort­mund main station to the stop "Dort­mund Kampstraße". From there, take U43 or U44 to the stop "Dort­mund Wittener Straße". Switch to bus line 447 and get off at "Dort­mund Uni­ver­si­tät S".

The H-Bahn is one of the hallmarks of TU Dort­mund Uni­ver­sity. There are two stations on Cam­pus Nord. One ("Dort­mund Uni­ver­si­tät S") is directly located at the suburban train stop, which connects the uni­ver­si­ty directly with the city of Dort­mund and the rest of the Ruhr Area. Also from this station, there are connections to the "Technologiepark" and (via Cam­pus Süd) Eichlinghofen. The other station is located at the dining hall at Cam­pus Nord and offers a direct connection to Cam­pus Süd every five minutes.

The AirportExpress is a fast and convenient means of transport from Dort­mund Airport (DTM) to Dort­mund Central Station, taking you there in little more than 20 minutes. From Dort­mund Central Station, you can continue to the uni­ver­si­ty campus by interurban railway (S-Bahn). A larger range of in­ter­na­tio­nal flight connections is offered at Düsseldorf Airport (DUS), which is about 60 kilometres away and can be directly reached by S-Bahn from the uni­ver­si­ty station.

The facilities of TU Dort­mund Uni­ver­sity are spread over two campuses, the larger Cam­pus North and the smaller Cam­pus South. Additionally, some areas of the uni­ver­si­ty are located in the adjacent "Technologiepark".

Site Map of TU Dort­mund Uni­ver­sity (Second Page in English).